Rac1 Regulates Neuronal Polarization through the WAVE Complex

Neuronal migration and axon growth, key events during neuronal development, require distinct changes in the cytoskeleton. Although many molecular regulators of polarity have been identified and characterized, relatively little is known about their physiological role in this process. To study the physiological function of Rac1 in neuronal development, we have generated a conditional knock-out mouse, in which Rac1 is ablated in the whole brain. Rac1 -deficient cerebellar granule neurons, which do not express other Rac isoforms, showed impaired neuronal migration and axon formation both in vivo and in vitro . In addition, Rac1 ablation disrupts lamellipodia formation in growth cones. The analysis of Rac1 effectors revealed the absence of the Wiskott–Aldrich syndrome protein (WASP) family verprolin-homologous protein (WAVE) complex from the plasma membrane of knock-out growth cones. Loss of WAVE function inhibited axon growth, whereas overexpression of a membrane-tethered WAVE mutant partially rescued axon growth in Rac1 -knock-out neurons. In addition, pharmacological inhibition of the WAVE complex effector Arp2/3 also reduced axon growth. We propose that Rac1 recruits the WAVE complex to the plasma membrane to enable actin remodeling necessary for axon growth.

CYRI (FAM49) proteins are local inhibitors of Scar/WAVE induced lamellipodia that bind directly to active Rac1

Neuronal polarization: From spatiotemporal signaling to cytoskeletal dynamics - ScienceDirect

Rac1 Regulates Neuronal Polarization through the WAVE Complex

Cells, Free Full-Text

The role of small GTPases in neuronal morphogenesis and polarity - Gonzalez‐Billault - 2012 - Cytoskeleton - Wiley Online Library

Rac1 and Rac3 GTPases and TPC2 are required for axonal outgrowth and migration of cortical interneurons, Journal of Cell Science

Cortical interneuron development: a role for small Rho GTPases

STK25 and MST3 Have Overlapping Roles to Regulate Rho GTPases during Cortical Development

PDF] Crucial polarity regulators in axon specification.

Neuronal actin cytoskeleton gain of function in the human brain - eBioMedicine

Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice

Frontiers Crosstalk between the Rho and Rab family of small GTPases in neurodegenerative disorders

Coronin 2B Regulates Neuronal Migration via Rac1-Dependent Multipolar–Bipolar Transition

Rac1 Regulates Neuronal Polarization through the WAVE Complex